Impaired hepatic glycogenolysis related to hyperinsulinemia in newborns from hyperglycemic pregnant rats.
We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.
Jame
P
P
Laboratoire de Physiologie du Développement, URA CNRS 307, Université Paris, France.
Ktorza
A
A
Bihoreau
M T
MT
Nurjhan
N
N
Ferré
P
P
Girard
J
J
Picon
L
L
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood; D006943:Hyperglycemia / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008112:Liver Glycogen / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D005934:Glucagon